Reducing Heavy Drinking to Optimize HIV/AIDS Treatment and Prevention

项目摘要/摘要 很少有治疗方法被评估以减少酗酒、酗酒和依赖的影响 感染艾滋病毒的病人身上。这些水平的酒精消费与减少对 高效抗逆转录病毒疗法(HAART)，增加病毒突变的可能性，增强疾病 进展，促进肝脏损伤，增加性行为风险。纳曲酮与纳曲酮联合应用 咨询是治疗酗酒、酗酒和依赖的有效方法，但目前还没有数据 关于它在艾滋病毒感染患者中的使用或疗效。这项拟议的研究比较了纳曲酮和安慰剂在24名患者中的作用。 HAART未依从性HIV感染患者的周随机双盲安慰剂对照临床试验 因酗酒、酗酒或依赖(N=154)在艾滋病毒诊所就诊。要确定长期的 影响治疗效果，所有患者将在9个月和12个月进行随访。患者随机服用纳曲酮 最初会收到口服的每日配方，如果耐受，将转移到每月延长 释放剂型。所有患者都将接受药物管理咨询平台(MM) 结合药物指导(MC)(MM/MC)。MM/MC是一种复合手工化治疗，旨在 大约适合在艾滋病毒初级保健环境中实施的治疗类型。它 通过一系列简要介绍，重点关注减少酗酒(MM)和提高服药依从性(MC) 由受过医学培训的提供者提供的干预。将对以下意图进行数据分析： 治疗样本随机分为纳曲酮+MM/MC组和安慰剂+MM/MC组。这个 主要研究结果是坚持使用HAART药物。二次研究结果包括 酗酒、HIV病毒变异(使用标准化验和超深度测序)、CD4改变 淋巴细胞计数和HIV核糖核酸、酒精-HAART肝毒性和性危险行为。这部小说 这项提议的方面包括：1)综合现场酒精和艾滋病毒治疗；2)使用扩展的 释放纳曲酮，这可能会改善服药患者的依从性 坚持是具有挑战性的；3)使用几种措施来遵守HAART，包括药房续药 数据；4)使用尖端技术检查新病毒突变的发展情况，包括 检测新的微小变异；以及5)收集有关治疗对肝脏影响的详细数据。这个 由一组经验丰富的艾滋病毒和成瘾研究人员进行的拟议研究将有助于确定这一角色 纳曲酮和循证咨询在HAART非依从性酒精问题受试者中的应用。

PROJECT SUMMARY/ABSTRACT Few treatments have been evaluated to reduce the impact of heavy drinking, alcohol abuse and dependence on HIV-infected patients. These levels of alcohol consumption are associated with decreased adherence to highly active antiretroviral therapy (HAART), an increased likelihood of viral mutations, enhanced disease progression, promotion of liver injury, and increased sexual risk taking. Naltrexone, when combined with counseling, is an effective treatment for heavy drinking, alcohol abuse and dependence yet there are no data on its use or efficacy in HIV-infected patients. The proposed study compares naltrexone to placebo in a 24- week randomized double-blind placebo-controlled clinical trial in HAART-non-adherent HIV-infected patients with heavy drinking, alcohol abuse or dependence (N=154 ) in an HIV clinic. To determine the long-term impact of treatment, all patients will undergo follow-up at 9 and 12 months. Patients randomized to naltrexone will initially receive the oral daily formulation and, if tolerated, will be transferred to the monthly extended release formulation. All patients will receive the counseling platform of Medication Management (MM) combined with Medication Coaching (MC) (MM/MC). MM/MC is a compound manualized treatment intended to approximate the type of treatment that would be suitable for implementation in an HIV primary care setting. It focuses on reducing heavy drinking (MM) and improving medication adherence (MC) through a series of brief interventions delivered by a medically trained provider. Data analyses will be conducted on the intention to treat sample of patients randomly assigned to receive naltrexone + MM/MC versus placebo + MM/MC. The primary study outcome is adherence to HAART medications. Secondary study outcomes include frequency of heavy drinking, HIV viral mutations (using standard assays and ultra-deep sequencing), change in CD4 lymphocyte counts and HIV RNA, alcohol-HAART hepatotoxicity, and sexual risk behaviors. The novel aspects of this proposal include: 1) Integrated on-site alcohol and HIV treatment; 2) The use of extended release naltrexone which is likely to improve adherence in this patient population for whom medication adherence is challenging; 3) The use of several measures for HAART adherence including pharmacy refill data; 4) The use of sophisticated techniques for examining the development of new viral mutations including the detection of new minor variants; and 5) Collection of detailed data on the hepatic effects of treatment. The proposed study, conducted by an experienced team of HIV and addiction researchers, will help define the role of naltrexone and evidence-based counseling in HAART-non-adherent subjects with alcohol problems.